Project Summary In this proposal, we request funding for the purchase of a multiphoton microscope system to be housed in the Beckman Institute for Advanced Science and Technology at the University of Illinois. The state-of-the-art microscopy system will permit deep-tissue imaging into fixed and live tissues and serve as a shared resource for multiple investigators at the University of Illinois. The microscope will be outfitted with an extended infrared laser, optogenetic stimulation capability and an easily moveable stage to permit in vitro as well as in vivo electrophysiology experimentation. In addition, the microscope will be supported and managed by the Beckman Institute Microscopy Suite, for which there is already dedicated space and full-time Ph.D.-level staff to manage the instrument. The microscopy suite is a unit that is fully supported by the Beckman Institute, with paid staff who have extensive experience in managing high-end laser- based microscopy systems. The Microscopy Suite also has infrastructure to ensure maximal utilization of the microscope by NIH-funded users. Eleven major users and one minor user have been identified, and their diverse interests represent the interdisciplinary nature of the Beckman Institute. The major users come from 8 different departments and use of a multiphoton microscope will support their NIH-supported research, with funding coming from 8 different institutes (NCI, NIAID, NIBIB, NIDA, NIDCD, NIMH, NIGMS and NINDS). The major users have research interests in developing novel technology platforms for cancer diagnosis, for understanding the biological underpinnings of inherited cognitive disorders, for understanding invertebrate neurobiology, studying glial-neuronal interactions and others. Therefore, the multiphoton microscope would support both basic and translational research across a variety of disciplines, and support ongoing NIH-funded research at Illinois.